Toxoplasma gondii is a serious health problem in newborns and in immunocompromised patients. This application proposes structural studies on the hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT), a central enzyme in the parasite s purine salvage pathway. X-ray crystallographic techniques will be used to generate high- resolution crystal structures of various conformational states of the enzyme and analyze site-directed mutants of the protein to gain a full understanding of the structure - function relationships in phosphoribosyltransfer catalysis. The atomic coordinates obtained for these structures will be exploited to computationally screen small molecule data bases with the DOCK3.5 suite of programs, and novel ligands will be discovered by these searches and evaluated biochemically as inhibitors of the HGXPRT enzyme. Computationally discovered high affinity inhibitors of HGXPRT that are toxic to T. gondii may serve as lead compounds for structure-based drug development.